Cysteamine (HS—CH2—CH2—NH2) is able to cross cell membranes easily due to its small size. At present, cysteamine is FDA-approved for the treatment of cystinosis, an intra-lysosomal cystine storage disorder. In cystinosis, cysteamine acts by converting cystine to cysteine and cysteine-cysteamine mixed disulfide which are then both able to leave the lysosome through the cysteine and lysine transporters respectively (Gahl et al., N Engl J Med 2002; 347(2):111-21). Treatment with cysteamine has been shown to result in lowering of intracellular cystine levels in circulating leukocytes (Dohil et al., J. Pediatr 148(6):764-9, 2006).
Impurities can be present in cysteamine formulations due to byproduct formation during the manufacturing process and/or due to modification (e.g., degradation) during storage of the drug product. Accurate and complete determination of the purity of cysteamine-containing formulations is important in securing marketing approval for the pharmaceutical product and in demonstrating that the pharmaceutical product has acceptable impurity levels for human administration at the time of release and that it has acceptable storage stability. Analysis of the purity of cysteamine-containing formulations using an HPLC method with an electrochemical detection system has proven not to have the sensitivity required to detect certain impurities found in cysteamine formulations.
The present invention provides improved methods for analyzing purity of compositions comprising cysteamine and detecting impurities in cysteamine compositions.